On a biophysical and mathematical model of Pgp-mediated multidrug resistance: understanding the "space-time" dimension of MDR.

Multidrug resistance (MDR) is explained by drug transporters with a drug-handling activity. Despite much work, MDR remains multifaceted, and several conditions are required to generate drug resistance. The drug pumping was conceptually described using a kinetic, i.e., temporal, approach. The re-emergence of physical biology has allowed us to take into account new parameters focusing on the notion of space. This, in turn, has given us important clues regarding the process whereby drug and transporter interact. We will demonstrate that the likelihood of drug-transporter meeting (i.e., the affinity) and thus interaction are also driven by the mechanical interaction between drug molecular weight (MW) and the membrane mechanical properties. This should allow us to mechanically control drug delivery.